Nishio K, Saijo N
Gan To Kagaku Ryoho. 1994 Feb;21(3):289-94.
An anticancer agent, cisplatin (CDDP), induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as P34cdc2 protein kinase. P34cdc2 kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC-9 cells. Evidence for a phosphorylated p34cdc2 complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 appeared to be dephosphorylated at M phase. After exposure to CDDP in G1 phase, PC-9 cells were arrested at G2 phase. The activation of p34cdc2 was inhibited by CDDP. Cyclin A, B and wee-1 kinase were not affected by the exposure to CDDP. Our data suggested that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34cdc2. We hypothesize that inhibition of p34cdc2 dephosphorylation by CDDP is important for its growth-inhibiting properties.
一种抗癌药物顺铂（CDDP）可诱导人PC-9癌细胞发生G2期阻滞。为阐明CDDP如何作用于细胞周期调控，我们分析了CDDP对细胞周期调节因子如P34cdc2蛋白激酶的影响。在同步化的PC-9细胞中，P34cdc2激酶活性在G2期最高，在G2/M转换后降低。从G2期细胞中获得了与细胞周期蛋白B复合的磷酸化p34cdc2的证据，并且p34cdc2在M期似乎发生了去磷酸化。在G1期暴露于CDDP后，PC-9细胞停滞在G2期。CDDP抑制了p34cdc2的激活。细胞周期蛋白A、B和wee-1激酶不受CDDP暴露的影响。我们的数据表明，CDDP对细胞周期阶段的影响可能受p34cdc2去磷酸化的调节。我们推测，CDDP对p34cdc2去磷酸化的抑制对其生长抑制特性很重要。
